A major goal of this proposed research is to elucidate the mechanism(s) which are responsible for producing skin lesions in pemphigus. Our approach involves studying the interaction of the pemphigus autoantibody with human epidermal cells in vitro, either in whole skin organ culture or in isolated epidermal cells in suspension culture. We will utilize techniques of biochemistry, histology, electron microscopy and immunology in an attempt to define this interaction in terms of the kinetics, role of complement, tertiary structural requirements of the autoantibody, effects on quantitative and qualitative protein synthesis, cellular viability and the nature of the observed partitioning of newly synthesized proteins from an insoluble to a soluble phase. Similar studies will also be conducted using skin from patients with various other skin diseases. We will also investigate the effects of other cell surface-interacting agents on epidermal cells, including antiblood group antibodies, burn serum autoantibodies and plant lectins. We will attempt to isolate and characterize the pemphigus and bullous pemphigoid antigens using techniques of affinity chromatography and gel exclusion column chromatography. Studies are proposed which deal with the nature of the newly synthesized collagens from cultured normal or diseased fibroblasts. Fibroblasts from normal or diseased tissues will be examined for synthesis of types I and III collagens and for alpha chain modifications at the level of the glycosylated hydroxylysyl residues.